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Intermittent fasting and obesity-related health outcomes: umbrella review of meta-analyses of randomized clinical trials

Umbrella review of 11 meta-analyses (130 RCTs) grading IF effects on obesity-related outcomes: many statistically significant pooled associations, but only one high-GRADE link (modified alternate-day fasting ~1–2 months for BMI reduction); fat-free mass emerged as a downside signal.

Design

  • Umbrella review of meta-analyses of RCTs through 12 Jan 2021
  • Included umbrella corpus: 11 meta-analyses describing 104 unique associations (130 underlying RCTs; median sample size 38, median follow-up 3 months)
  • Interventions classed as IF: alternate-day fasting, modified ADF, 5:2, and time-restricted eating
  • Evidence grading: GRADE (high / moderate / low / very low)

Headline quantitative narrative (abstract)

  • 28/104 associations (27%) reached statistical significance favouring IF for endpoints including BMI, body weight, fat mass, LDL-C, TC, TG, FPG, fasting insulin, HOMA-IR, and BP
  • High-quality evidence supported one significant association: modified alternate-day fasting (1–2 months) → moderate BMI reduction vs regular diet in healthy / overweight / obesity / NAFLD populations
  • Moderate-quality evidence: 6 associations (6%)
  • Among significant findings, most were very low (72%) or low (21%) GRADE in authors' accounting
  • Fat-free mass: IF associated with reduced fat-free mass (interpret lean-mass preservation cautiously)

Evidence hygiene

  • Umbrella-of-meta-analyses tier—use next to window-eating RCTs on time-restricted-eating and intermittent-fasting primary papers, not as a replacement for isocaloric control discipline.

Publication

Patikorn C, Roubal K, Veettil SK, et al. JAMA Netw Open. 2021 Dec 1;4(12):e2139558. PMID 34919135.

Outcomes

  • Across 104 graded associations, 28 (27%) reached statistical significance for beneficial cardiometabolic/anthropometric directions; only 1 association carried high GRADE (modified ADF 1–2 months for BMI reduction).
  • Authors report intermittent fasting associated with reduced fat-free mass among umbrella-graded outcomes—lean-mass preservation caveat for prolonged protocols.
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